Invasive aspergillosis in a renal transplant recipient successfully treated with interferon-gamma.

Invasive aspergillosis is a serious complication of solid organ transplantation. An early diagnosis is hampered by the lack of reliable serum markers and, even if appropriately diagnosed and treated with current antifungal agents, has a high mortality rate. We report a case of invasive pulmonary and cerebral aspergillosis in a renal transplant patient treated with IFN-γ in conjunction with combination anti-fungal therapy for six weeks in whom complete resolution of the fungal infection was achieved. Renal function remained intact throughout the treatment period. Surveillance CT scans of the chest and head showed resolution of prior disease but revealed a new left upper lobe mass four months after completion of treatment with IFN-γ. Biopsy of the lesion was positive for primary lung adenocarcinoma, for which she underwent left upper lobe resection. The pathology report confirmed clear surgical margins and lymph nodes and no evidence of fungal hyphae. IFN-γ should be considered early in the management of invasive aspergillosis in renal transplant patients. To date, allograft rejection has not been encountered.

Taxol-induced apoptosis in human SKOV3 ovarian and MCF7 breast carcinoma cells is caspase-3 and caspase-9 independent.

Taxol is used in chemotherapy regimens against breast and ovarian cancer. Treatment of tumor model cell lines with taxol induces apoptosis, but exact mechanism is not sufficiently understood. Our results demonstrate that in response to taxol, various cell types differentially utilize distinct apoptotic pathways. Using MCF7 breast carcinoma cells transfected with caspase-3 gene, we showed that taxol-induced apoptosis occurred in the absence of caspase-3 and caspase-9 activation. Similar results were obtained with ovarian SKOV3 carcinoma cells, expressing high level of endogenous caspase-3. In contrast, staurosporine-induced apoptosis in these cells was accompanied by proteolytic cleavage of pro-caspase-3 and induction of caspase-3 enzymatic activity. The effect of taxol appears to be cell type-specific, since taxol-induced apoptosis in leukemia U937 cells involved caspase-3 activation step. We conclude that a unique caspase-3 and caspase-9 independent pathway is elicited by taxol to induce apoptosis in human ovarian and breast cancinoma cells.

Aurintricarboxylic acid decreases proliferative potential of SKOV3 and MCF7 human carcinoma cells.

The effect of aurintricarboxylic acid (ATA) on cell growth and proliferative capacity was studied in human ovarian SKOV3 and breast MCF7 carcinoma cells. ATA moderately inhibited cell growth measured by a Neutral red assay after a 24-hour incubation of the cells in the presence of ATA. The ATA-treated cells displayed a markedly decreased capacity to proliferate, as was evident from a colony formation assay. The initial and delayed anti-proliferative effects of ATA were dose-dependent. Together, the results indicated that ATA offers the potential of being recognized as an anti-tumor drug, at least in certain types of cancers.

The role of ERK 1/2 and p38 MAP-kinase pathways in taxol-induced apoptosis in human ovarian carcinoma cells.

Taxol is an anticancer agent of natural origin with significant activity against a number of human cancers including ovarian and breast carcinomas. Its cytotoxic activity has been attributed to its ability to stabilize microtubules and to promote microtubule assembly. Recently it has become clearer that Taxol has additional activities including effects in cell signaling and gene expression. We have shown previously that Taxol activates ERK 1/2 MAP-kinases and results in the formation of GRB2/SHC complexes in murine macrophage-like RAW 267.4 cells. Here we demonstrate that Taxol activates ERK 1/2 and p38 MAP-kinases in human ovarian carcinoma cells with distinct kinetics. Activation of ERK1/2 has been observed at low concentrations of Taxol (1-100 nM) within 0.5-6 h, whereas longer exposure(24 h) to nanomolar concentrations of Taxol resulted in an abrogation of the ERK1/2 phosphorylation/activation. Higher concentrations (1-10 microM) resulted in a sharp inhibition of ERK1/2 activity. p38 kinase was activated by high concentrations (1-10 microM) of Taxol within 2 h and remained active for more than 24 h. The kinetic studies showed that these effects of Taxol coincided with an inhibition of proliferation, and the onset of apoptosis. The appearance of the fragmented chromatin visualized by DAPI staining, and DNA fragments seen on an agarose gel, coincided with the decrease in ERK1/2 activation and concomitant increase of the level of active p38 MAPK. The inhibitor PD98059 abrogated ERK 1/2 activation and increased the cytotoxic effect of Taxol. An inhibitor of p38 kinase, SB203580, protected the cells partially from Taxol and, unexpectedly, activated ERK 1/2 kinases. We conclude that the alternative use of ERK1/2 and p38 MAP-kinase pathways may be necessary for the transition from proliferation state to Taxol-induced apoptosisin human ovarian carcinoma cells.

The changing paradigm of sexually transmitted disease control in the era of managed health care.

Several trends in sexually transmitted diseases (STDs) have laid the foundation for a new paradigm for STD treatment and prevention that encompasses a community-wide, population-oriented approach. Public health STD programs, in partnership with a wide variety of community collaborators, will need to carry out the essential functions of public health-assessment, policy development, and assurance-by developing resources for community organizing and planning, enhanced information systems, and comprehensive training programs for professional staff and community partners. Community providers (particularly practicing clinicians and community and hospital clinics) will need to deliver primary prevention (community health promotion and clinical preventive services) and secondary prevention (screening and treatment) services while categorical STD clinics focus on providing care for high-risk, high-frequency STD transmitters who serve as the reservoir for much of a community's bacterial STDs. Managed care organizations and public health STD programs will need to formalize collaborative arrangements and capitalize on the strengths of each organization in order to have a population-level impact on STD transmission.

Preventive services in a Medicare managed care environment.

The results of a four year demonstration project of preventive services for Medicare managed care enrollees suggest that health promotion programs can impact health behaviors and outcomes. The study provided selected preventive services to 1,800 Medicare enrollees in a managed care environment. Participants were randomly assigned to control and experimental groups with the experimental group receiving an intervention service package and the control group usual care. The results included enhanced health behavior practices, lower depression, and higher immunization rates among those individuals in the experimental group. This study suggests that selected preventive services can be provided in a managed care environment to Medicare enrollees with likely positive health status and utilization outcomes.

Glial transforming growth factor (TGF)-beta isotypes in multiple sclerosis: differential glial expression of TGF-beta 1, 2 and 3 isotypes in multiple sclerosis.

We studied glial transforming growth factor (TGF)-beta isotype expression in 14 cases of multiple sclerosis. Acute active lesions exhibited selective TGF-beta 2 immunoreactivity of lesion encircling ramified microglia. In contrast, astrocytes within chronic active white matter lesions expressed all three isotypes. Chronic active lesions which extended into cortex exhibited selective cortical astrocyte TGF-beta 2 expression. This isotype was also selectively expressed by astrocytes in apparently normal white matter. A similar pattern of glial TGF-beta expression was seen in the pathological control, progressive multifocal leukoencephalopathy. The results suggest that TGF-beta cytokines are locally expressed in demyelination and that the beta 2 isotype may be uniquely regulated.

Identifying depressive symptoms among elderly Medicare HMO enrollees.

Increasing attention has been devoted to the urgent need for identifying depressive symptomatology at the primary care point of contact for older individuals to prevent more serious disease and potential negative behavioral outcomes. Delivering medical care services in a system that is sensitive to the symptoms of depression may lead to greater cost-effectiveness and improved quality of life. This paper examines the correlates of depression in a random sample of 1800 Medicare beneficiaries enrolled in a risk-sharing HMO. Ten percent of the total sample reported a high degree of depressive symptoms, as measured by the CES-D score. The prevalence of depressive symptoms was significantly higher for those who were not married, reported less well-developed social support networks, had low perceived ability to control future health, or had poorer health status. Depressive symptoms were also associated with a greater number of physician office visits and higher ambulatory charges, although no significant relationship was found for inpatient use or total charges. Practical approaches to monitoring depressive symptomatology at the primary care level in an HMO are suggested.

Experimental immunization with Borrelia burgdorferi induces development of antibodies to gangliosides.

Patients with neuroborreliosis produce antibodies, mostly of the immunoglobulin M (IgM) class, to gangliosides, particularly to those with Gal(beta 1-3)GalNac terminal sequences. Lewis rats were immunized with a nonpathogenic strain of Borrelia burgdorferi and with a chloroform-methanol extract (nonprotein) of this organism (CM) to determine whether antibodies to B. burgdorferi also recognized gangliosides. Rats were also immunized with asialo-GM1 to determine whether the elicited antibodies recognized antigens in B. burgdorferi. Rats immunized with B. burgdorferi produced low levels of IgM antibodies that cross-reacted with asialo-GM1 and GM1. Rats immunized with CM had marked IgM reactivity to asialo-GM1 and GM1. Immunization with asialo-GM1 resulted in antibodies that cross-reacted with B. burgdorferi antigens. Although antibodies to B. burgdorferi were of both the IgM and IgG classes, those to CM and to asialo-GM1 and GM1 were predominantly in the IgM fraction. Reactivity of the IgM antibodies decreased after adsorption with the heterologous and the homologous antigens, indicating bidirectional cross-reactivity between CM, asialo-GM1, and GM1 and that immunization with one produces antibodies to the other. There was no in vivo deposition of Ig in peripheral nerves, nor was there nerve pathology as a result of immunizations, but IgM antibodies to asialo-GM1 and CM recognized homologous antigens in the nodes of Ranvier of peripheral nerves from nonimmunized rats. This immunization model suggests that antibodies to gangliosides in Lyme disease have a microbial origin and are potentially relevant in pathogenesis.

In situ detection of polymerase chain reaction-amplified HIV-1 nucleic acids in skeletal muscle in patients with myopathy.

The purpose of this study was to determine if the myopathy that commonly occurs in patients with AIDS is associated with active HIV-1 infection in the muscle tissues. Seven muscle biopsies from patients infected by HIV-1 and six controls were tested for HIV-1 DNA and RNA using polymerase chain reaction in situ hybridization and reverse transcriptase in situ polymerase chain reaction. HIV-1 DNA was detected in rare cells in only one case by standard in situ hybridization. However, after polymerase chain reaction amplification HIV-1 DNA was detected in many cells in four of seven muscle tissues from patients with the viral infection and in none of the controls. The number of cells with detectable provirus in the tissue positive by standard in situ hybridization increased up to 100-fold after amplification. Most of the HIV-1 infected cells were macrophages, as determined by colabeling experiments that were localized mainly in the areas of myocyte necrosis. Myocyte nuclei that contained amplified HIV-1 nucleic acids were also noted. Most virally infected cells contained HIV-1 transcripts, which is consistent with activated infection. The demonstration of many HIV-1 infected macrophages and myocytes in muscle biopsies from HIV-1 infected patients with myopathy suggests that active viral infection may play a role in the clinical disease state.

A comparison of the recovery period for women and men after an acute myocardial infarction.

OBJECTIVES: To compare return to work, participation in cardiac rehabilitation, and sexual activity in women and men recovering from acute myocardial infarction (AMI). DESIGN: A descriptive survey design was used. Descriptive statistics and chi square analysis were used to compare differences between women and men after an AMI. SETTING: The survey was mailed to the subject's home. SUBJECTS: A purposive sample of 20 women and 42 men. RESULTS: Comparing women with men, there were significant differences in the following activities with women evidencing higher percentages in responsibility for household duties before AMI, and cooking, washing dishes, reading, bed making, laundry, dusting and sweeping within 4 weeks after AMI. For those subjects who were sexually active before AMI, all resumed sexual activities after an average of 8 weeks. Women reported a decrease in frequency, less satisfactory relationship, and more reports of chest pain during sexual activity. Subjects reported that nurses gave little or no counseling concerning resumption of household activities, return to work issues, and sexual activity. Women received less counseling than men after AMI. CONCLUSIONS: The findings are not generalizable to the population at large; however, the study indicates a need to investigate further the recovery period for women who experience AMI.

L-tryptophan-associated eosinophilia-myalgia syndrome: perspective of a new illness.

The current knowledge of the eosinophilia-myalgia syndrome as an evolving new disease entity is reviewed in the context of previously described eosinophilic disorders. The acute and chronic manifestations parallel the findings of the toxic oil syndrome of Spain and include scleroderma-like skin disease, neuropathy, and myopathy.

Paraganglioma of the cauda equina: case report with magnetic resonance imaging description.

The case of a 35-year-old white man with a cauda equina syndrome is presented. Magnetic resonance imaging confirmed the diagnosis, and radiation treatment successfully treated the condition.

The neuromuscular pathology of the Eosinophilia-Myalgia syndrome.

The Eosinophilia-Myalgia Syndrome (EMS) is a recently reorganized disorder in patients ingesting pharmacologic doses of L-tryptophan. We studied the lesions of skeletal muscle, peripheral nerve and skin in 12 cases of EMS. Perimyositis was severe in four, moderate in two, mild in three and absent in three cases. The lesions contained many eosinophils, T-helper cells, mast cells and activated macrophages. Type 2 myofiber atrophy was present in five cases and in one, this was the only pathologic finding. Severe epineurial inflammation was seen in the three sural nerve biopsies. Indirect evidence for peripheral neurologic involvement in three other cases consisted of inflammation surrounding intramuscular nerve twigs (two cases) and neurogenic atrophy (one case). Phlebitis accompanied the connective tissue inflammation in five cases and endarteritis in one. Fasciitis was present in three of four skin biopsies and dermal fibrosis in one.

Trends in hospital deductions from revenue. Increases in uncompensated care and payment adjustments.

The 1980s produced tighter restrictions on Medicaid eligibility, greater reluctance among insurers to cover small groups, and increased price competition, resulting in a larger percentage of unreimbursed charges. Here the authors use financial data from a cross-section of California hospitals to explore the extent and variation of such deductions from revenue.

Cutaneous manifestations of the L-tryptophan-associated eosinophilia-myalgia syndrome: a spectrum of sclerodermatous skin disease.

The natural history of the clinical and pathologic features of skin disease was reviewed prospectively in 30 patients with the L-tryptophan-associated eosinophilia-myalgia syndrome. Overall, cutaneous manifestations developed in 26 patients (87%). Early lesions were nonspecific and characterized predominantly by an erythematous macular eruption on the trunk and extremities. The most characteristic abnormality noted was the spectrum of sclerodermatous disease in 15 patients (50%) often after a subacute stage of peripheral or truncal edema. Clinical and/or biopsy evidence of eosinophilic fasciitis was seen in nine patients (30%). Findings consistent with diffuse, limited, or localized scleroderma were subsequently observed in nine patients (33%). Small mucinous papules, similar to those seen in scleromyxedema, were found in five patients (17%). Alopecia, frequently a late sequela, developed in 11 (37%). Common histologic features included papillary dermal fibrosis, dermal and fascial infiltrates consisting of mononuclear cells and eosinophils, deposition of glycosaminoglycans in the dermis, and, in some patients, numerous mast cells.

L-tryptophan-associated eosinophilic perimyositis, neuritis, and fasciitis. A clinicopathologic and laboratory study of 25 patients.

We have described the spectrum and prevalence of the clinical and laboratory manifestations of a multisystem disorder associated with the ingestion of L-tryptophan. At least 3 subsets of clinical disease have been identified: 1) a neuromuscular disorder which may present with myalgias and mild weakness and then progress to quadriparesis related to an axonal neuropathy and interstitial myositis (perimyositis), 2) a syndrome of eosinophilic fasciitis with characteristic cutaneous induration, and 3) the Löffler syndrome consisting of pulmonary infiltrates with eosinophilia. Corticosteroids may be useful for patients with the Löffler syndrome and offer only a modest benefit in the majority of patients with neuromuscular disease. The clinical course appears to be chronic, and the long-term sequelae of this disorder are unknown. The etiologic agent remains undetermined; however, studies are in progress to examine the mechanism of eosinophilia, appropriate therapeutic intervention, and the long-term outcome of the affected individuals.

Eosinophilic neuritis, perimyositis, and vasculitis associated with ingestion of L-tryptophan.

Four cases are described of a clinical syndrome which developed in the setting of L-tryptophan ingestion. The major manifestations consisted of myalgias, neuropathy, weakness, and profound eosinophilia. Pathologically a vasculitis involving predominantly small veins was observed along with a mixed cellular infiltrate in the perimysium and epineurium. Clusters of eosinophils were characteristically noted in the tissue specimens. The clinical course appears to be chronic although further longterm followup will be required. One patient pursued a relentless downhill course with progressive neurologic impairment and death. Although the mechanism of tissue injury in these individuals is speculative, the possible association of this widely used nonprescription medication with this syndrome should be recognized.